Iron

Delayed (1-2 days) infusion reaction (including arthralgia, back pain, chills, dizziness, and fever) may occur with large doses (eg, total dose infusion) of IV iron dextran; usually subsides within 3-4 days. May also occur (less commonly) with IM administration; subsiding within 3-7 days.

[U.S. Boxed Warning]: Deaths associated with parenteral administration following anaphylactic-type reactions have been reported (use only where resuscitation equipment and personnel are available). A test dose should be administered to all patients prior to the first therapeutic dose. Anaphylactic and other hypersensitivity reactions have occurred even in patients who tolerated the test dose; observe for anaphylactic reactions during any iron dextran administration; fatalities have occurred with the test dose. A history of drug allergy (including multiple drug allergies) and/or the concomitant use of an ACE inhibitor may increase the risk of anaphylactic-type reactions. Adverse events (including life-threatening) associated with iron dextran usually occur more with the high-molecular-weight formulation (Dexferrum), compared to low-molecular-weight (INFeD) (Chertow, 2006). Disease-related concerns:

Use with caution in patients with a significant history of allergies or asthma.

In patients with cancer-related anemia (either due to cancer or chemotherapy-induced) requiring iron supplementation, the IV route is superior to oral therapy; IM administration is not recommended for parenteral iron supplementation.

Use with caution in patients with pre-existing cardiovascular disease; iron dextran may exacerbate cardiovascular complications.

Use with extreme caution in patients with serious hepatic impairment.

In patients with chronic kidney disease (CKD) requiring iron supplementation, the IV route is preferred for hemodialysis patients; either oral iron or IV iron may be used for nondialysis and peritoneal dialysis CKD patients. Avoid use during acute kidney infection.

Use with caution in patients with rheumatoid arthritis; may exacerbate joint pain and swelling. Special populations:

Anemia in the elderly is often caused by “anemia of chronic disease” or associated with inflammation rather than blood loss. Iron stores are usually normal or increased, with a serum ferritin >50 ng/mL and a decreased total iron binding capacity. IV administration of iron dextran is often preferred over IM in the elderly secondary to a decreased muscle mass and the need for daily injections.

Intramuscular iron dextran use in neonates may be associated with an increased incidence of gram-negative sepsis. Dosage form specific issues:

Iron dextran products differ in chemical characteristics. The high-molecular-weight formulation (Dexferrum) and the low-molecular-weight formulation (INFeD) are not clinically interchangeable. Other warnings/precautions:

[U.S. Boxed Warning]: Use only in patients where the iron deficient state is not amenable to oral iron therapy. Discontinue oral iron prior to initiating parenteral iron therapy.

Intramuscular injections of iron-carbohydrate complexes may have a risk of delayed injection site tumor development.

Exogenous hemosiderosis may result from excess iron stores; patients with refractory anemias and/or hemoglobinopathies may be prone to iron overload with unwarranted iron supplementation.